Atherosclerosis 220 (2012) 552–556 Contents lists available at SciVerse ScienceDirect Atherosclerosis journa l h omepa g e: www.elsevier.com/locate/atherosclerosis Increased plasma levels of NGAL, a marker of neutrophil activation, in patients with abdominal aortic aneurysm Priscila Ramos-Mozo a , Julio Madrigal-Matute a , Melina Vega de Ceniga b , Luis Miguel Blanco-Colio a , Olivier Meilhac c , Laurent Feldman c , Jean-Baptiste Michel c , Paula Clancy d , Jonathan Golledge d , Paul E. Norman e , Jesus Egido a , José Luis Martin-Ventura a,∗ a Vascular Research Lab, IIS, Fundación Jimenez Diaz, Autonoma University, Madrid, Spain b Vascular Surgery, Hospital Galdakao-Usansolo, Bilbao, Spain c Inserm, U698, Univ Paris 7, CHU X-Bichat, Paris, France d Vascular Biology Unit, School of Medicine and Dentistry, James Cook University, Townsville 4811, Australia e School of Surgery, University of Western Australia, Perth, Australia a r t i c l e i n f o Article history: Received 18 May 2011 Received in revised form 26 October 2011 Accepted 16 November 2011 Available online 25 November 2011 Keywords: Abdominal aortic aneurysm Biomarkers Polymorphonuclear neutrophils Neutrophil gelatinase-associated lipocalin Intraluminal thrombus a b s t r a c t Objective: Neutrophil gelatinase-associated lipocalin (NGAL) plasma concentrations have been associated with cardiovascular diseases. We aimed to assess the association of NGAL with abdominal aortic aneurysm (AAA). Methods: NGAL concentrations were analyzed by Western blotting in conditioned medium of polymor- phonuclear neutrophils (PMNs) from AAA patients (n = 22) and controls (n = 11), and also in aortic biopsies from AAA patients and healthy controls (n = 10). Plasma NGAL concentrations were measured by ELISA in three groups of subjects from France (n = 60), Spain (n = 75) and Australia (n = 100) and associated with AAA presence and growth. Results: PMNs isolated from AAA patients secreted significantly greater amounts of NGAL than PMNs from controls. Luminal thrombus released large amounts of NGAL compared to abluminal AAA thrombus, AAA wall and healthy aortic media. Plasma NGAL concentrations were significantly higher in patients with AAA than controls from France [115 (78–200) vs. 94 (72–114) ng/ml, p < 0.001]. NGAL plasma concentrations in AAA patients from Spain correlated with other markers of thrombus activity (plasmin–antiplasmin complexes and D-dimer). Furthermore, a positive correlation between plasma NGAL and retrospective AAA growth (rho = 0.4, p = 0.01) was observed, which remained significant after adjusting for other risk factors. Plasma NGAL was only weakly associated with prospective growth in both Spanish and Australian patients. Conclusions: NGAL is released by PMNs and by the luminal part of AAA thrombus. NGAL plasma levels were increased in AAA patients compared with healthy subjects and correlated with retrospective AAA growth. Further studies in larger subjects groups are needed to confirm the association between NGAL and AAA presence and growth. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Abdominal aortic aneurysm (AAA) is an important health prob- lem in the elderly. In cross-sectional studies the prevalence of AAA varies from 3% to 8% in men aged >65 years. In elderly men AAA may cause as much as 2–3% of all deaths [1]. ∗ Corresponding author at: Vascular Research Lab, IIS, Fundación Jiménez Diaz, Autonoma University, Av. Reyes Católicos 2, 28040 Madrid, Spain. Tel.: +34 915504800; fax: +34 915442636. E-mail address: jlmartin@fjd.es (J.L. Martin-Ventura). Human AAAs are characterized by the presence of intraluminal thrombus (ILT), an important source of proteolytic and oxidative enzymes implicated in AAA [2,3]. Polymorphonuclear neutrophils (PMNs), along with platelets and red blood cells, are particularly abundant within the luminal layer of AAA thrombus. PMNs may contribute to two main mechanisms of AAA evolution, namely medial destruction and adventitial immune-inflammatory pro- cesses [4,5]. A role for PMNs in the pathogenesis of AAA is supported by recent studies in animal models of AAA [6,7]. PMN depletion is able to inhibit experimental AAA formation [7] and short-term preoperative doxycycline therapy improves the proteolytic balance in human AAA, possibly through limiting aortic wall neutrophil 0021-9150/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2011.11.023